Molecular Genetics of Influenza haemagglutinin production: Developing a rational basis for optimising vaccine yield

Pandemic influenza presents a major threat to global public health. The ideal approach to countering this threat would be to develop a vaccine to prevent the disease. Unfortunately, however, because there are so many different types of influenza virus constantly circulating in humans and animals, and because the virus can mutate easily and quickly, scientists can?t predict exactly what the next pandemic virus will look like. It is not currently possible, therefore, to prepare in advance a vaccine that is guaranteed to work against any pandemic threat. For this reason, research scientists are trying to find ways of speeding up the process of developing and producing a vaccine once a pandemic has begun. An important part of this is maximising vaccine production capacity since during an outbreak, tens of millions of vaccine doses would need to be produced each week to have an impact on the first wave of disease. Influenza virus vaccines are produced in eggs and so the number of vaccine doses that can be produced from a given number of eggs is crucial. We know that this yield is quite variable depending on the particular virus strain that is used for vaccine production, but we don?t know why. This research project aims to understand the reasons behind this variable yield and to use this knowledge to find ways of developing high yielding vaccine strains that will help manufacturers produce the maximum possible number of vaccine doses in the shortest possible time when a pandemic strikes.

Vaccine production against pandemic strains of influenza virus depends crucially on rapid development of attenuated virus strains which are safe to put into large scale production but that also produce good yields of vaccine antigen in eggs, the principal basis for influenza vaccine production. Recent work at NIBSC and other laboratories has revealed that properties apparently inherent in the haemagglutinin and/or neuraminidase genes of currently circulating avian H5N1 strains result in low yields of antigen during production, in spite of the fact that these strains grow to high titres in eggs. Since global influenza vaccine manufacturing capacity is already well short of that needed to deal with a pandemic, any reduction in yield will have a huge public health impact. The research programme aims to investigate the genetic basis for the low yield phenomenon in current H5 strains and to provide a basis for rapidly creating robust, high yielding vaccine strains in the event of future pandemic emergencies.